The overall objective of this research program has been to identify and characterize the actions of the central neurotransmitter and neuropeptide systems that regulate the secretion of luteinizing hormone (LH) and prolactin (PRL) from the anterior pituitary gland in response to physiological stimuli. Studies conducted during the current funding period have demonstrated that one role of NPY in lactation is to amplify the inhibitory action of DA over PRL secretion, through a specific reduction in the entry of extracellular Ca2+ via L-type calcium channels. Because lactation is also characterized by a marked physiological hyperphagia, and because NPY is the most powerful central stimulant of feeding behavior, one set of proposed experiments will test the hypothesis that the NPY neurons of the arcuate nucleus also mediate the hyperphagia associated with lactation. Using a variety of approaches, the proposed experiments will investigate whether acute disruption of NPY transmission by central antiNPY immunoneutralization, antisense oligonucleotides or peptide antagonists of NPY decrease food intake during lactation and will test whether the Y1 and/or Y5 receptor mediates this action of NPY in lactation. A second major objective is to identify the physiological signal(s) responsible for the up-regulation of hypothalamic NPY during lactation. The proposed studies will test the hypothesis that the hypoinsulinemia associated with lactation increases the expression of NPY in the hypothalamus. These studies will test the effects of systemic insulin treatment of lactating rats on hypothalamic preproNPY mRNA levels, NPY peptide concentrations and NPY immunoreactivity, and will examine whether interruption of nursing, which reduces hypothalamic NPY expression, also alters circulating insulin concentrations. To test whether leptin might also be involved in the up-regulation of NPY in the arcuate-paraventricular-dorsomedial hypothalamic feeding network, a third set of studies will assess the effects of central leptin administration to lactating rats on hypothalamic pre proNPY mRNA levels, NPY tide concentrations and NPY immunoreactivity in the hypothalamus.